Dynamically changing effects of corticosteroids on human hippocampal and prefrontal processing

Hum Brain Mapp. 2012 Dec;33(12):2885-97. doi: 10.1002/hbm.21409. Epub 2011 Sep 21.


Stress has a powerful impact on memory. Corticosteroids, released in response to stress, are thought to mediate, at least in part, these effects by affecting neuronal plasticity in brain regions involved in memory formation, including the hippocampus and prefrontal cortex. Animal studies have delineated aspects of the underlying physiological mechanisms, revealing rapid, nongenomic effects facilitating synaptic plasticity, followed several hours later by a gene-mediated suppression of this plasticity. Here, we tested the hypothesis that corticosteroids would also rapidly upregulate and slowly downregulate brain regions critical for episodic memory formation in humans. To target rapid and slow effects of corticosteroids on neural processing associated with memory formation, we investigated 18 young, healthy men who received 20 mg hydrocortisone either 30 or 180 min before a memory encoding task in a double-blind, placebo-controlled, counter-balanced, crossover design. We used functional MRI to measure neural responses during these memory encoding sessions, which were separated by a month. Results revealed that corticosteroids' slow effects reduced both prefrontal and hippocampal responses, while no significant rapid actions of corticosteroids were observed. Thereby, this study provides initial evidence for dynamically changing corticosteroid effects on brain regions involved in memory formation in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affect / physiology
  • Brain Mapping
  • Cross-Over Studies
  • Double-Blind Method
  • Heart Rate / physiology
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Humans
  • Hydrocortisone / analysis
  • Hydrocortisone / pharmacology*
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiology
  • Saliva / chemistry


  • Hydrocortisone